新技术或为治疗不孕不育带来革命性突破


导读:近日发表于国际杂志Biomicrofluidics上的一篇研究论文中,来自台湾清华大学等处的研究人员为了使得试管受精技术更加有效,其开发了一种新技术,其可以在受精卵植入到女性体内之前使得胚胎有效地生长及进行筛选,这或许可以帮助促进被植入胚胎的靶向选择,增加试管受精的成功率,进而降低花费。




早在许多年前,获得诺贝尔奖的体外受精法(试管受精)为许多不孕不育家庭带来了福音,然而由于该方法非常耗时、昂贵而且在女性成功怀孕前需要进行多个周期;在美国一个周期平均价格高达1.2万美金,因此对于许多夫妻而言该技术是遥不可及的。


而近日发表于国际杂志Biomicrofluidics上的一篇研究论文中,来自台湾清华大学等处的研究人员为了使得试管受精技术更加有效,其开发了一种新技术,其可以在受精卵植入到女性体内之前使得胚胎有效地生长及进行筛选,这或许可以帮助促进被植入胚胎的靶向选择,增加试管受精的成功率,进而降低花费。


研究者Chihchen Chen教授说道,我们开发的新技术可以有效减少受精的周期循环数以及胚胎移植的次数,这样就可以大大降低夫妻的压力水平,目前我们非常感兴趣去理解促进胚胎发育以及改善胚胎培养的必要物质以及原理;体外受精的胚胎通常会集聚在小的液滴中,随后被植入母体子宫内;在一系列群体中对胚胎进行营养供给是非常必要的,但这往往会使得胚胎移植变得不再具有选择性,而目前研究者还不能很容易地评估在微滴中单一胚胎的活力。


于是研究人员开发了一种新技术在微孔板中培养小鼠胚胎,使其扩散到微孔板中以便每一个孔都包含有1个或2个胚胎,随后给微孔板上覆以矿物油来抑制胚胎在微孔板的不同孔中移动,这就可以使得移液器进入系统中最终将胚胎吸入成功转移至子宫内,这种微孔系统可以给每一个胚胎提供特有的环境,帮助研究者逐个进行筛选最终确定哪个胚胎最具有活力。


Chen说道,胚胎对于环境非常敏感,理解胚胎所处的微环境可以促进胚胎的生长,最大化地降低对胚胎的遗传操作;我们利用高分辨率的延时成像技术追踪了小鼠胚胎的发育过程,有意思的是,当在微孔板中进行培养时,胚胎可以成功发育成囊胚;当胚胎发育到4细胞及8细胞阶段所花费的时间就可以帮助准确预测其后期发育成为囊胚的可能性,从而就为筛选最具潜力及最适宜进行移植的胚胎提供了很大帮助,而靶向性的移植策略或可降低整个过程所需的卵细胞的数量,从而间接地减少了资金和时间的花费。


研究者表示,我们利用小鼠胚胎进行了初期的实验研究,我们希望该研究工作有一天对人类不孕不育的研究具有一定的临床意义,我们相信通过更为深入的研究最终可以将该技术成功应用于人类的试管受精中。


推荐原文摘要:Microwells support high-resolution time-lapse imaging and development of preimplanted mouse embryos.


Biomicrofluidics  doi:10.1063/1.4918642


Yu-Hsiang Chung1, Yi-Hsing Hsiao1, Wei-Lun Kao1, Chia-Hsien Hsu2, Da-Jeng Yao1 and Chihchen Chen1,a)


A vital aspect affecting the success rate of in vitro fertilization is the culture environment of the embryo. However, what is not yet comprehensively understood is the affect the biochemical, physical, and genetic requirements have over the dynamic development of human or mouse preimplantation embryos. The conventional microdrop technique often cultures embryos in groups, which limits the investigation of the microenvironment of embryos. We report an open microwell platform, which enables micropipette manipulation and culture of embryos in defined sub-microliter volumes without valves. The fluidic environment of each microwell is secluded from others by layering oil on top, allowing for non-invasive, high-resolution time-lapse microscopy, and data collection from each individual embryo without confounding factors. We have successfully cultured mouse embryos from the two-cell stage to completely hatched blastocysts inside microwells with an 89% success rate (n?=?64), which is comparable to the success rate of the contemporary practice. Development timings of mouse embryos that developed into blastocysts are statistically different to those of embryos that failed to form blastocysts (p–value?<?10?10, two-tailed Student's t-test) and are robust indicators of the competence of the embryo to form a blastocyst in vitro with 94% sensitivity and 100% specificity. Embryos at the cleavage- or blastocyst-stage following the normal development timings were selected and transferred to the uteri of surrogate female mice. Fifteen of twenty-two (68%) blastocysts and four of ten (40%) embryos successfully developed into normal baby mice following embryo transfer. This microwell platform, which supports the development of preimplanted embryos and is low-cost, easy to fabricate and operate, we believe, opens opportunities for a wide range of applications in reproductive medicine and cell biology.


来源于:转化医学网

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